Chronic hypertension is associated with resistance artery remodelling and mechanical alterations. However, the contribution of elastin has not been thoroughly studied. Our objective was to evaluate the role of elastin in vascular remodelling of mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR). MRA segments from Wistar Kyoto rats (WKY) and SHR were pressurised under passive conditions at a range of physiological pressures with pressure myography. Confocal microscopy was used to determine differences in the quantity and organisation of elastin in intact pressure‐fixed arteries. To assess the contribution of elastin to MRA structure and mechanics, myograph‐mounted vessels were studied before and after elastase incubation. When compared with WKY, MRA from SHR showed: (1) a smaller lumen, (2) decreased distensibility at low pressures, (3) a leftward shift of the stress‐strain relationship, (4) redistribution of elastin within the internal elastic lamina (IEL) leading to smaller fenestrae but no change in fenestrae number or elastin amount. Elastase incubation (1) fragmented the structure of IEL in a concentration‐dependent fashion, (2) abolished all the structural and mechanical differences between strains, and (3) decreased distensibility at low pressures. The study shows the overriding role of elastin in determining vascular dimensions and mechanical properties in a resistance artery. In addition, it informs hypertensive remodelling. MRA remodelling and increased stiffness are accompanied by elastin restructuring within the IEL and elastin degradation reverses structural and mechanical alterations of SHR MRA. Differences in elastin organisation are, therefore, a central element in small artery remodelling in hypertension.

TLR expression is associated with prostate cancer with recurrence and the role of TLR receptors in the biology of malignancy merits study. Therapeutic strategies to boost or block TLRs may be of interest.

1 Recent evidence supports additional subtypes of vasodilator b-adrenoceptor (b-AR) besides the 'classical' b 2 . The aim of this study was to investigate the distribution of b-ARs in the wall of rat mesenteric resistance artery (MRA), to establish the relative roles of b-ARs in smooth muscle and other cell types in mediating vasodilatation and to analyse this in relation to the functional pharmacology. 2 We first examined the vasodilator b-AR subtype using 'subtype-selective' agonists against the, commonly employed, phenylephrine-induced tone. Concentration-related relaxation was produced by isoprenaline (pEC 50 : 7.7070.1) (b 1 and b 2 ). Salbutamol (b 2 ), BRL 37344 (b 3 ) and CGP 12177 (atypical b) caused relaxation but were 144, 100 and 263 times less potent than isoprenaline; the 'b 3 -adrenoceptor agonist' CL 316243 was ineffective. 3 In arteries precontracted with 5-HT or U 46619, isoprenaline produced concentration-related relaxation but salbutamol, BRL 37344, CGP 12177 and CL 316243 did not. SR 59230A, CGP 12177 and BRL 37344 caused a parallel rightward shift in the concentration-response curve to phenylephrine indicating competitive a 1 -AR antagonism, explaining the false-positive 'vasodilator' action against phenylephrine-induced tone. Endothelial denudation but not L-NAME slightly attenuated isoprenaline-mediated vasodilatation in phenylephrine and U 46619 precontracted MRA.

BACKGROUND: Extracellular matrix metalloproteases (MMPs) have raised an extraordinary interest in cancer research because of their potential role in basal membrane and extracellular matrix degradation, consequently facilitating tumour invasion and metastases development. METHODS: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs 1, 2, 7, 9, 11, 13, 14, and their tissue inhibitors, TIMPs 1, 2 and 3. More than 2600 determinations on cancer specimens from 133 patients with clinically localised prostate carcinoma, 20 patients with prostatic intraepithelial neoplasia and 50 patients with benign prostate hyperplasia and controls, were performed. RESULTS: When compared with benign pathologies, prostate carcinomas had higher expression of all MMPs and TIMPs. Dendogram shows a first-order division of tumours into two distinct MMPs/TIMPs molecular profiles, one of them with high MMPs/TIMs expression profile (n ¼ 70; 52.6%). Tumours with high expression of MMP-11 or -13, or cluster thereof, were significantly associated with higher probability of biochemical recurrence. The prevalence of prostate cancer is so high that it could be considered as a normal age-related phenomenon (Hughes et al, 2005). Several published autopsy series have shown that up to one-third of men between the ages of 30 and 40 years harbour histological evidence of prostate carcinoma (Sakr et al, 1994).A significant minority of patients undergoing radical prostatectomy for clinical organ-confined disease will ultimately be found to have pathological evidence of spread outside the prostate. Although these patients may be expected to have progression and survival rates comparable to those of patients with clinical advanced clinical disease, as defined by grade and serum prostatespecific antigen (PSA) level, those men who present with clinical stage T3 are likely to have greater tumour volume, higher grade and increased likelihood of regional spread. Currently, the majority of men undergoing prostatectomy for pathologically advanced disease are categorised as high risk on the basis of serum PSA value or biopsy Gleason score. Nevertheless, there is some overlap in the groups of men undergoing radical prostatectomy for clinical stage T3 and for pathological stage T3 (Meng and Carrol, 2007).Despite recent improvement in diagnostic and therapeutic techniques, the survival rate of prostate cancer patients remains poor due to post-treatment recurrence disease. Despite all the recent efforts in the identification of molecular mechanisms involved in the progression of prostate cancer, tumour progression in the prostatic compartment, as well as in the metastasis compartment, is poorly understood (Logothetis and Lin, 2005). These pitfalls underscore the need for new risk markers that allow the early detection of carcinogenesis and, therefore, of cancer relapse.Degradation of the stromal connective tissue and basement membrane components are key elements in tumour invasion and metastasis. This is particularly true wi...

We have previously developed a method for estimating elastin content and organization in resistance arteries, where it is a minor component. The aim of the present study was to validate the method against a quantitative assay and to determine the relative importance of elastin content and organization for intrinsic elasticity of small arteries. Mesenteric third order branches (from 10-day-old, 1-and 6-month-old rats) and middle cerebral arteries (from 6-month-old rats) were pressurized. β-Values were calculated from stress-strain relationships and used as indicators of intrinsic stiffness. The same pressure-fixed arteries were used to estimate elastin content and organization in the internal elastic lamina with confocal microscopy. Collagen and elastin contents were determined by Picrosirius Red staining and radioimmunoassay for desmosine, respectively. Confocal and desmosine assays gave similar results: no difference in elastin content of mesenteric vessels from 1-and 6-month-old rats, and a significant reduction in cerebral compared to mesenteric arteries. For all parameters (elastin and collagen content, fenestrae area and internal elastic lamina thickness) the best correlation was found between β-values and fenestrae size. These data suggest that in small arteries: (1) confocal microscopy can be used as a method for the simultaneous study of changes in elastin content and organization; and (2) elastin organization might be a key determinant of intrinsic elastic properties.